New Zealand Data Sheet APO-MOCLOBEMIDE 1. APO-MOCLOBEMIDE (150mg and 300mg film coated tablets) 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Moclobemide 150mg Moclobemide 300mg Chemical Structure: Molecular Formula: C13H17CIN2O2 Excipient with known effect Apo Moclobemide is gluten and lactose free. For a full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM APO-MOCLOBEMIDE 150mg tablets are oval, biconvex tablets, film coated yellow and identified APO over 150 on one side and scored on the other. Each tablet contains 150mg moclobemide and typically weighs 402mg. APO-MOCLOBEMIDE 300mg tablets are white, oval, biconvex, film coated tablets identified APO over 300 on one side and scored on the other. Each tablet contains 300mg moclobemide and typically weighs 400mg. 4. CLINICAL PARTICULARS 4.1 Therapeutic indications Apo-Moclobemide is indicated in the treatment of depressive syndromes and social phobia. Please refer to Medsafe website (www.medsafe.govt.nz) for the most recent datasheet Page 1 of 12 APO-MOCLOBEMIDE 4.2 Dose and method of administration Dose Apo-Moclobemide should be taken after meals. The dose does not need to be specially adjusted in elderly patients or patients with impaired renal function. When hepatic function is severely impaired or inhibited by medication that inhibits microsomal mixed function oxidase e.g. cimetidine, the daily dose should be reduced to half or one third. Depressive syndromes: The recommended daily dose range is 300-600mg. Treatment with moclobemide can begin with the full therapeutic dose of 300-450mg daily taken in two or three divided doses. With severe depression the dose can be increased to 600mg/day. The dose should not be increase until after the first week, as bioavailability increases during this period. The individual response may allow a reduction in the daily dose. Treatment should continue for at least 4-6 weeks in order to assess efficacy. Social phobia: The recommended daily dose is 600mg given in 2 divided doses. Treatment with 600mg/day should continue for 8-12 weeks in order to assess the efficacy of the medicine. Social phobia may be a chronic condition and it is reasonable to consider continuation of treatment for a person responding to treatment. Long-term study results indicate that the efficacy of treatment with moclobemide is maintained with continued use. Periodic evaluation of patients is recommended to establish if further treatment is required. Use in Children and Adolescents (under 18 years of age): Safety and efficacy have not been established in this population. Consequently, moclobemide should not be used in patients under 18 years of age (see Special Warnings and Precautions). Method of administration See dose. 4.3 Contraindications • Known hypersensitivity to moclobemide • Acute confusional states • Co-administration with selegiline • Moclobemide should not be used in paediatrics, as clinical experience of the medicines action in children is lacking. • Co-administration with clomipramine should be avoided due to the risks of increased incidence of adverse effects. Please refer to Medsafe website (www.medsafe.govt.nz) for the most recent datasheet Page 2 of 12 APO-MOCLOBEMIDE 4.4 Special warnings and precautions for use Clinical Worsening and Suicide Risk: Patients of any age with Major Depressive Disorder may experience worsening of their depression and/or the emergence of suicidal ideation and behaviour (suicidality), whether or not they are taking antidepressive medications, and this risk may persist until significant remission occurs. Patients should be closely monitored, especially at the beginning of therapy or when the dose is changed, until improvement occurs. There has been a long-standing concern that some antidepressants may have a role in the emergence of suicidality in some patients. The possible risk of increased suicidality in patients applies to all classes of antidepressant medicines, as available data are not adequate to exclude this risk for any antidepressant. Therefore, consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse or whose emergent suicidality is severe, abrupt in onset, or was not part of the patient’s presenting symptoms. Generally, when stopping an antidepressant, doses should be tapered rather than stopped abruptly. The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility (aggressiveness), impulsivity, akathisia (psychomotor restlessness), hypomania, and mania have been reported in adult and paediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and non- psychiatric. Although a causal link between emergence of such symptoms and either the worsening or depression and/or the emergence of suicidal impulses has not been established, consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients for whom such symptoms are severe, abrupt in onset, or were not part of the patients presenting symptoms. Because of the possibility of co-morbidity between major depressive disorder and other psychiatric and non-psychiatric disorders, the same precautions observed when treating patients with major depressive disorder should be observed when treating patients with other psychiatric and non-psychiatric disorders. Mania and Bipolar Disorder: A major depressive episode may be the initial presentation of bipolar disorder. It is generally believed (though not established in controlled trials) that treating such an episode with any antidepressant alone may increase the likelihood of a mixed/manic episode in patients at risk for bipolar disorder. Prior to initiating treatment with an antidepressant, patients should be adequately screened to determine if they are at risk for bipolar disorder. It should be noted that Moclobemide is not approved for use in treating bipolar depression. Excitation / Agitation: Depressed patients with excitation or agitation as the main clinical feature may require the addition of benzodiazepines. Please refer to Medsafe website (www.medsafe.govt.nz) for the most recent datasheet Page 3 of 12 APO-MOCLOBEMIDE Schizophrenic symptoms: Moclobemide therapy may exacerbate the schizophrenic symptoms of depressive patients with schizophrenic or schizoaffective psychoses. Therapy with long-acting neuroleptics should be continued in such patients, if possible. Dietary Restrictions: Special dietary restrictions are not generally required with Moclobemide therapy. However, hypersensitivity to tyramine may exist in some patients and patients should be advised to avoid the consumption to large amounts of tyramine-rich foods. Hypersensitivity: Symptoms of hypersensitivity reactions may occur and include rash and oedema. Theoretical pharmacological considerations indicate that MAO inhibitors may precipitate a hypertensive reaction in patients with thyrotoxicosis or pheochromocytoma. Because experience with Moclobemide therapy in this population group is lacking, caution should be exercised with regard to prescribing Apo-Moclobemide. Additional medicines which enhance serotonin e.g. many other antidepressants, particularly in multiple combinations, should be given with caution. This is particularly true for clomipramine (see Contraindications, Section 4.3). Cardiac disorders: Cases of QTc prolongation and Torsades de Pointes (TdP), have been reported in association with excessive doses of moclobemide. Therefore moclobemide should be used with caution in patients with risk factors for QTc prolongation including congenital long QT syndrome, age >65 years, female sex, structural heart disease/LV dysfunction, medical conditions such as renal or hepatic disease, use of medicines that inhibit the metabolism of moclobemide, and the concomitant use of othet QTc prolonging medicines (see Interaction with other medicines and other forms of interaction, Section 4.5). Hypokalaemia and hypomagnesaemia should be corrected prior to treatment. Information for Patients and Families: Patients and their families should be alerted about the need to monitor for the emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia, hypomania, mania, worsening of sedression, and suicidal ideation, especially early during antidepressant treatment. Such symptoms should be reported to the patient’s doctor, especially if they are severe, abrupt in onset, or were not part of the patient’s presenting symptoms. The patient has the right to treatment meeting appropriate ethical and professional standards, and the patient needs to be fully informed with frank discussion of risk/benefit issues relating to this medicine’s efficacy and safety when used in the treatment regimen proposed. Please refer to Medsafe website (www.medsafe.govt.nz) for the most recent datasheet Page 4 of 12 APO-MOCLOBEMIDE 4.5 Interaction with other medicines and other forms of interaction Dextromethorphan Isolated cases of severe, central nervous system adverse reactions (giddiness, light- headedness and agitation) have been reported after co-administration of moclobemide and dextromethorphan. Since some cough and cold medicines may contain dextromethorphan, they should not be taken without prior consultation with a physician. Selegiline Co-administration of moclobemide and selegiline is contraindicated due to the relative loss of selectivity